239 research outputs found
Mathematical Models of Meal Amount and Timing Variability With Implementation in the Type-1 Diabetes Patient Decision Simulator
No full textBackground: In type 1 diabetes (T1D) research, in-silico clinical trials (ISCTs) have proven effective in accelerating the development of new therapies. However, published simulators lack a realistic description of some aspects of patient lifestyle which can remarkably affect glucose control. In this paper, we develop a mathematical description of meal carbohydrates (CHO) amount and timing, with the aim to improve the meal generation module in the T1D Patient Decision Simulator (T1D-PDS) published in Vettoretti et al. Methods: Data of 32 T1D subjects under free-living conditions for 4874 days were used. Univariate probability density function (PDF) parametric models with different candidate shapes were fitted, individually, against sample distributions of: CHO amounts of breakfast (CHOB), lunch (CHOL), dinner (CHOD), and snack (CHOS); breakfast timing (TB); and time between breakfast-lunch (TBL) and between lunch-dinner (TLD). Furthermore, a support vector machine (SVM) classifier was developed to predict the occurrence of a snack in future fixed-length time windows. Once embedded inside the T1D-PDS, an ISCT was performed. Results: Resulting PDF models were: gamma (CHOB, CHOS), lognormal (CHOL, TB), loglogistic (CHOD), and generalized-extreme-values (TBL, TLD). The SVM showed a classification accuracy of 0.8 over the test set. The distributions of simulated meal data were not statistically different from the distributions of the real data used to develop the models (α = 0.05). Conclusions: The models of meal amount and timing variability developed are suitable for describing real data. Their inclusion in modules that describe patient behavior in the T1D-PDS can permit investigators to perform more realistic, reliable, and insightful ISCTs
Trattamento dell’iperuricemia nel paziente nefropatico: è giunto il momento di agire?
No full textNumerosi studi epidemiologici condotti nella popolazione generale indicano che l’iperuricemia si associa ad un incremento del rischio di sviluppare insufficienza renale. Inoltre, tra i soggetti che sono già affetti da una malattia renale cronica (MRC), l’iperuricemia si associa sia ad una più rapida progressione di malattia sia ad un significativo incremento della mortalità e degli eventi cardiovascolari. Tuttavia, ad oggi il ruolo causale dell’iperuricemia nel determinare l’insorgenza e la progressione del danno renale e cardiovascolare non è ancora completamente accertato, per cui le indicazioni al trattamento farmacologico dell’iperuricemia asintomatica nei pazienti con MRC sono ancora affidate all’orientamento personale del singolo medico. Al fine di stabilire se sia possibile esprimere un orientamento clinico basato sull’evidenza abbiamo eseguito un’analisi comparativa degli studi prospettici che hanno valutato l’impatto della terapia ipouricemizzante con inibitori della xantino ossidasi (IXAO) rispetto all’insorgenza e alla progressione del danno renale. Inoltre, dal momento che in passato nei soggetti con funzionalità renale ridotta il trattamento con IXAO è stato associato ad un elevato rischio di tossicità, abbiamo analizzato la tossicità di questi farmaci per vari gradi compromissione della funzione renale riassumendo indicazioni, controindicazioni e dosi consigliate nei pazienti affetti da MRC. In fine, a conclusione della nostra analisi abbiamo elaborato un algoritmo finalizzato ad orientare le decisioni cliniche in merito al trattamento dell’iperuricemia nei soggetti affetti da MRC.Numerous epidemiological studies conducted in the general population indicate that hyperuricemia is associated with an increased risk of developing renal failure. Moreover, among those subjects who are already suffering from chronic kidney disease (CKD), hyperuricemia is associated with a more rapid progression of disease besides with an increased risk of mortality and cardiovascular events. However, to date, the causal role of hyperuricaemia in determining the onset and progression of cardiovascular and renal damage is not yet fully established. Therefore the indications for pharmacological treatment of hyperuricemia (and particulary of asymptomatic hyperuricemia) in patients with CKD are still assigned to the personal orientation of the physician. In order to produce an evidence-based clinical appraisal on this topic, we performed a comparative analysis that included all the prospective studies that have evaluated the impact of treatment with xanthine oxidase inhibithors (XOI) with respect to the onset and progression of CKD. Moreover, since in the past the treatment with XOI was associated with a high risk of toxicity in patients with impaired renal function, we analyzed the toxicity of these drugs for various degrees of renal function impairment summarizing indications, contraindications and recommended doses in patients affected by CKD. In the end, as conclusion of our analysis, we propose an algorithm aimed at guiding the clinical decisions about the treatment of hyperuricemia in patients with CKD
Prevention and treatment of diabetic nephropathy: the program for irbesartan mortality and morbidity evaluation
No full textMid-Term Blood Glucose Prediction: A Hybrid Approach Using Grammatical Evolution and Physiological Models
No full textMolecular dynamics and docking studies on RSV fusion protein as tools for discovery of new inhibitors
No full textImportance of blood pressure control in chronic kidney disease
No full textArterial hypertension together with proteinuria is one of the most important factors associated with the progression of both diabetic and nondiabetic chronic kidney disease. In this review, the role of hypertension and proteinuria in renal disease progression, the BP target that should be achieved to slow the progression of renal damage, and the influence of baseline and current proteinuria on the renoprotective effects of antihypertensive therapy are discussed thoroughly. The interaction between the renoprotective effects of specific antihypertensive agents--mostly angiotensin-converting enzyme inhibitors and angiotensin receptor blockers--and the level of achieved BP also are evaluated. The body of evidence provided by several studies emphasizes the importance of both lowering BP and inhibiting the renin-angiotensin system as specific goals for renal and cardiovascular protection in chronic kidney diseas
Patients with Hypertensive Nephropathy and Chronic Kidney Disease Might Not Benefit from Strict Blood Pressure Control
No full textBACKGROUND/AIMS:
In patients with chronic kidney disease (CKD) strict blood pressure (BP) control is reno-protective. However, renal benefits from BP control might depend also on the etiology of CKD. We investigated if maintenance of BP at target is equally effective in subjects with hypertensive nephropathy (HN+) and in those with other nephropathies (HN-).
METHODS:
We evaluated 148 patients with CKD (stages 3-5) in two visits at least 12 months apart. BP was measured both as office BP and 24h ambulatory blood pressure (ABP). Glomerular filtration rate (eGFR) was estimated with CKD-EPI formula. The slope of eGFR variation (ΔeGFR) was calculated as: (eGFR1-eGFR0)/months of follow up.
RESULTS:
Cohort characteristics were: HN-(n=82) and HN+ (n=66), age (71±9 vs 74±9 years; p=0.09); prevalence of diabetes (57 vs 43%; p=0.19); average follow up (19±7 vs 21±9 months; p=0.3). HN- and HN+ did not differ regarding both baseline eGFR (34±18 vs 35±14 ml/min; p=0.97) and ΔeGFR (0.00±0.53 vs -0.06±0.35 ml/min/month, p=0.52). The proportion of patients with BP at target at both visits was similar in HN- and HN+ (office BP: HN- 18% and HN+ 27%; p=0.21; ABP: HN- 42% and HN+ 43; p=0.96). In patients with office BP at target at both visits HN- showed a significant improvement of ΔeGFR respect to HN+ (HN-: 0.240 ± 0.395 and HN+: -0.140±0.313 ml/min/ month; p=0.026). In patients with office BP not at target HN- and HN+ did not show any difference in ΔeGFR (HN- 0.00±0.47; HN+ -0.030±0.420 ml/min/month; p=0.66). ABP was not associated with differences in ΔeGFR either if it was at target (HN- 0.104±0.383 and HN+ 0.00±0.476 ml/min/month; p=0.42) or not (HN- -0.057±0.503 and HN+ -0.092±0.325 ml/ min/month; p=0.87).
CONCLUSION:
In patients with CKD and HN+ maintenance of BP targets recommended by current guidelines is less reno-protective than it is in HN-
Modeling the error of factory-calibrated continuous glucose monitoring sensors: Application to Dexcom G6 sensor data
No full textMinimally-invasive continuous glucose monitoring (CGM) sensors are used in diabetes therapy to monitor interstitial glucose (IG) concentration almost continuously (e.g. every 5 min) and detect/predict dangerous hypo/hyperglycemic episodes. When compared with frequent blood glucose (BG) concentration references, CGM measurements are unavoidably affected by error. Models of the CGM error can be important in several applications, e.g. for testing in simulation the safety and effectiveness of CGM-based artificial pancreas algorithms. In this work, we model the error of the Dexcom G6, a CGM sensor that recently entered the market and does not require in vivo calibrations. The dataset includes CGM and BG data collected in 11 subjects wearing two Dexcom G6 sensors in parallel. The model is derived applying a methodology to dissect and model 3 main CGM error components: BG-to-IG kinetics, calibration error and measurement noise. An aspect of novelty of the method is its capability of handling factory-calibrated CGM sensor data. Results of model identification show that the time-variability of sensor calibration error during the sensor lifetime (10 days) can be well represented by a regression model with time-variant parameters described by 2nd-order polynomials in time
Hypertensive Congenital Adrenal Enzymatic Defects Detected By High-performance Liquid-chromatography of Corticosteroids
No full textThe simultaneous measurement of the adrenal deoxycorticosterone (DOC), 18-OH-DOC, corticosterone (B), 18-OH-B, 11-deoxycortisol (S) and cortisol (F) present in human plasma in cases of adrenal dysfunction was accomplished using a high-performance liquid chromatographic (HPLC) system with a UV detector and with a radioimmunoassay (RIA). After a solid-phase extraction, plasma samples were separated by HPLC using a gradient of water-acetonitrile-ethanol on a radial compressed reversed-phase column. In a 70-min cycle, a complete separation of adrenal steroids was accomplished. The UV detector allowed direct measurement of F in each plasma sample while in selected cases B and S were directly determined. It was therefore possible quickly to identify patients with hypertensive congenital adrenal enzymatic defects with this method: the 17-alpha-hydroxylase deficiency characterized by the absence of measurable levels of F with an evident peak corresponding to B and the 11-beta-hydroxylase deficiency in which high levels of S without F are detected. The RIA of DOC, B, 18-OH-DOC and 18-OH-B complete the characterization of the adrenal defect. Therefore, with this HPLC method it is possible to recognize the major hypertensive adrenal enzymatic deficiencies such as the defect of 17-alpha-hydroxylase or 11-beta-hydroxylase. With "RIA" detectors an almost complete spectrum of adrenal steroid secretion can be obtained
Spontaneous low-protein intake in older CKD patients: one diet may not fit all
No full textBackgroundProtein restriction has been extended to stage 3 chronic kidney disease (CKD) regardless of age in the latest K-DOQI guidelines for the dietary management of patients with CKD. However, in elderly CKD patients there is a tendency to a spontaneous reduction in protein and energy intake that may impair the overall nutritional status. The aim of our study is to assess whether there are differences in malnutrition, exercise capacity and inflammatory status in elderly CKD patients with spontaneously low protein intake (sLPI) compared with patients with normal protein intake (NPI).MethodsWe performed a cross-sectional analysis of 123 incident patients. Malnutrition was assessed using Malnutrition Inflammation Score (MIS) and serum markers; As for physical performance, we used Short Physical Performance Battery (SPPB) and handgrip strength.ResultsWe found that in older patients with advanced CKD, as many as 68% had low spontaneous protein intake, and they were more malnourished evaluated with MIS (25% vs. 10%, p = 0.033), protein-energy wasting (PEW) (43% vs. 14%, p = 0.002) and nPCR (0.63[0.51–0.69] vs. 0.95[0.87–1.1], p < 0.0001). They also had worse body composition, in terms of lower mid-arm muscular circumference (MAMC), fat tissue index (FTI) and higher overhydration (OH). sLPI patients also had higher levels of IL6 (4.6[2.9–8.9] vs. 2.8[0.8–5.1], p = 0.002). Moreover, sLPI patients were frailer (33% vs. 24%, p = 0.037) and had poorer physical performance especially when assessed with (SPPB) (7[5–9] vs. 9[7–10], p = 0.004) and gait test time (6.08 + 2 vs. 7.22 + 2.7, p = 0.04). sLPI was associated with lower physical performance [SPPB OR, 0.79 (0.46–0.97), p = 0.046] and malnutrition [MIS 1.6 (1.05–3.5), p = 0.041] independently from patients’ age and eGFR.ConclusionWe found that in older patients with advanced CKD, up to 68% had low spontaneous protein intake and were frailer, more malnourished and with lower physical performance. These findings emphasize the importance of assessing patients’ needs, and personalized approaches with individual risk–benefit assessments should be sought. To achieve the best possible outcomes, targeted interventions should use all available tools
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